Aberrant expression and/or signaling of some tyrosine kinase receptors have been recognized as important in carcinogenesis (Kolibaba and Druker, Biochim. Biophys. Acta. 1333:F217-248, 1997). To determine if a particular tyrosine kinase receptor carries prognostic value, many translational studies have used immunohistochemistry (IHC) to detect expression of the receptor in tumor specimens. While conventional IHC approaches are relatively easy to perform on materials that are readily available, they evaluate only one aspect of the receptor. When IHC was used to examine the expression of the epidermal growth factor receptor (EGFR) in head and neck squamous cell carcinomas (HNSCC), a strong association was noted between high EGFR expression and poor survival (Grandis et al., J. Natl. Cancer Inst. 90:824-832, 1998). However, EGFR staining was not predictive of advanced stage disease. Subsequent studies used either fluorescence resonance energy transfer (FRET) or phospho-specific IHC to measure EGFR phosphorylation in HNSCC. While there was a significant association between activated EGFR and disease-free survival, no correlation was found between phosphorylation and disease stage (Kong et al., Cancer. Res. 66:2834-2843, 2006; Hiraishi et al., Pathol. Oncol. Res. 12:87-91, 2006). In spite of the critical role of EGFR in HNSCC, its expression and phosphorylation are not the only determinants of aggressive disease. A recent study reported that 42% of HNSCC expressed the EGFR truncation mutant, EGFRvIII, where it contributes to enhanced growth and resistance to EGFR targeting by Erbitux® (Sok et al., Clin. Cancer Res. 12:5064-5073, 2006). Thus, the expression of EGFR variants may be another important aspect related to the role of EGFR in HNSCC. Few studies have examined EGFR status in primary pediatric tumors. Despite the readily detectable EGFR expression in primary neuroblastoma and a documented effect of gefitinib on different NBL cell lines, only certain patients have benefited from reversible EGFR inhibitors in clinical trials. There is a continuing need for diagnostic methods that allow more effective targeted therapies in cancer.